We’re lucky to have NICE guidelines in the UK. A couple of years ago, on a visit to the US, one of my collaborators from the US mentioned how jealous he was that we have them. His practice was to get a CT scan for everyone with a head injury. The NICE guidelines give us a framework for implementing evidence-based decision rules like the Canadian CT head and CHALICE rules on a widespread basis. One area I think the NICE guideline for head injury can improve, however, is for anticoagulated patients with minor head injury.

The NICE guideline suggests that we scan head injured anticoagulated patients who have lost consciousness or have amnesia. In the absence of other high risk features, however, the remainder of patients are potentially eligible for immediate discharge without even so much as an INR check. This makes me worry.

Unfortunately, the Canadian CT head rule can’t really help us out here because that study excluded patients with coagulopathy. The New Orleans rule didn’t exclude coagulopathic patients but their analysis was, shall we say, somewhat underpowered as they only had 1 patient with coagulopathy in the study! So what is the evidence behind managing head injury in anticoagulated patients?

Fortunately, we do have some evidence, although it’s relatively limited evidence if we’re honest. A case series of 144 patients demonstrated that the incidence of clinically important intracranial injury in warfarinised patients was 7%. For me, that’s a sufficient risk to prevent me from ruling out a bleed in this group and to make me want to request a CT brain. Roughly 7% of patients with chest pain who have a normal ECG are having an acute myocardial infarction. But I wouldn’t dream of ruling out AMI just because the ECG is normal. So neither should we consider ruling out intracranial haemorrhage at that level of risk.

What’s more, anticoagulated patients who develop an intracranial haemorrhage may not meet the NICE criteria for CT (which are based on the Canadian CT head rule, incidentally). This means that they can bleed despite being relatively asymptomatic. And a subtherapeutic INR doesn’t mean we can relax either, as shown in this great study from John Batchelor and Simon Rendell from my own institution.

OK, so we’re going to get a CT for these patients. I’ve sold you that, right? But if the CT’s normal, surely we can relax. Right?

This great small study from Annals of Emergency Medicine sheds some light on that situation. The authors implemented a protocol to immediately CT all warfarinised head injured patients, observe them for 24 hours, then re-scan them. Of 97 patients, 87 agreed to stay in for observation and have a repeat scan. 5 (6%) of those patients had a late bleed, not detected on the initial scan. OK, it was minimal in 2 patients. But 1 required craniotomy. What’s more, only 1 of those 5 patients had showed signs of neurological deterioration in the 24 hour period between scans. 2 further patients developed late bleeds even after a normal scan at 24 hours. So, this study definitely tells us that there’s an important incidence of late bleeding in anticoagulated patients. Not only do we need to strongly consider scanning these patients, but we also need to consider repeating the scan 24 hours later, even in the absence of neurological deterioration. What’s more, the symptoms reported by the patient may not be a great predictor of intracranial bleeding. Only 1 of the 6 who bled reported a severe headache, and only 1 was vomiting. If we rely on our patient becoming symptomatic during the period of observation, we may still miss some late bleeds.

Of course, this is just one study. Other studies do confirm that there’s an incidence of late bleeding in anticoagulated patients, although it may not be quite as high as 6%. However, what’s clear is that these patients ooze, and they ooze slowly. Of course, we don’t want to miss a bleed, if present, initially. Given the prevalence of bleeding at the time of presentation, I suggest that we should still scan these patients at presentation. But we should also be alert to the possibility of late bleeds.

From discussions on Twitter, I know that people are doing this after 6 hours rather than 24. There’s no evidence to definitively tell us which strategy is better. In my practice, I’ll be strongly considering an initial scan, an INR scan, a period of observation and a repeat scan after 24 hours. It’s not clear whether that’s the optimal strategy. What is clear is that we must be extremely careful with these patients. They bleed. And they bleed late.

So, what about reversal of the anticoagulation? Well, that’s a whole different debate – you’ll have to watch this space!…

The 14th International Conference on Emergency Medicine in Dublin has been one of the most tweeted about healthcare conferences in history. As we go into the final day, it seems fitting to set a Twitter challenge for the #ICEM2012 Tweeters.

Shortly after 2pm I will be presenting early results of a systematic review of high sensitivity troponin, using a lower cut-off than usual to exclude acute myocardial infarction. We recently published a paper suggesting that patients with initial high sensitivity troponin T <3ng/L could potentially have AMI ‘ruled out’ with high sensitivity and negative predictive value.

The results have stimulated significant debate as there is uncertainty about whether they should be implemented in practice. We therefore sought to systematically review the literature in order to determine whether our findings are consistent with those of other groups and to obtain pooled estimates of sensitivity and negative predictive value to narrow the confidence intervals.

The final slide of my presentation on 30th June will have an embedded Twitter feed, sourced from the hashtag #hsTnT. On the last day of such a successful conference for social media, let’s go out with a bang. Please feed into this experiment by commenting, questioning, discussing these findings and those of this blog using the hashtag #hsTnT. Your tweets will appear on my final slide and will feed the discussion at ICEM, which will in turn feed the discussion on Twitter.

Recently, I published a paper in the Journal of the American College of Cardiology describing a strategy that could rule out acute myocardial infarction (AMI) in over a quarter of patients using a single blood test at the point of presentation.

The strategy relies on the use of the high sensitivity troponin T assay from Roche Diagnostics. This assay has a 99th percentile (the diagnostic cut-off) of 14ng/L but the assay can detect levels way below that, in apparently healthy people. In fact, the assay can be reported down to 3ng/L, which is known as the limit of blank (LoB) of the assay.

We know that high sensitivity troponin assays can quantify levels of troponin below the 99th percentile but, at present, we don’t use that information clinically. It doesn’t matter whether the patient has completely undetectable levels of high sensitivity troponin T (<3ng/L) or levels of anything from 3 to 14ng/L. So long as the level is <14ng/L, it’s normal – and that’s all we need to know to rule out AMI.

Ever since high sensitivity assays became available, we’ve also known that they have a higher diagnostic sensitivity for AMI than previous generation troponin assays, i.e. more of the patients with AMI will have positive results when they first arrive at hospital. Unfortunately, the sensitivity still isn’t good enough to allow us to reassure patients that they’re not having a heart attack without repeating the test a number of hours later – at least, not using the conventional cut-off.

I wondered whether we could use the additional information from levels below the 99th percentile to enable us to rule out AMI in some patients immediately. It makes sense that, if troponin levels slowly begin to rise in the circulation after AMI, there should be detectable levels in the circulation even before the level exceeds the 99th percentile. Perhaps those patients who have absolutely no detectable troponin using this highly sensitive assay could be immediately reassured that they don’t have AMI.

Tobias Reichlin’s seminal publication in the New England Journal of Medicine in 2009 suggests that this strategy may have some mileage. In the online appendix, the sensitivity of high sensitivity troponin T (hs-cTnT) at the 3ng/L cut-off was 100%, i.e. no patients with initially undetectable (<3ng/L) levels had AMI.

We sought to validate that finding. In a prospective diagnostic cohort study, we had serum samples from 703 patients. Among these patients, a hs-cTnT level of <3ng/L had 100% sensitivity and negative predictive value for AMI. We then went on to audit our results after implementing hs-cTnT in the clinical environment. Among 915 patients who underwent 2 or more hs-cTnT tests during their admission at our institution (for any reason), only 1 patient with initially undetectable (<3ng/L) troponin developed a subsequent rise, giving a sensitivity of 99.4%. These findings formed the basis of the publication in the Journal of the American College of Cardiology, at http://www.ncbi.nlm.nih.gov/pubmed/21920261.

Having documented these findings, we were keen to determine whether they would stand up to prospective validation and could be introduced into practice to rule out AMI earlier and enable earlier reassurance for many patients, while reducing unnecessary hospital admissions. We therefore undertook a systematic review.

The systematic review is ongoing but early findings are to be presented at the International Conference on Emergency Medicine in June 2012. From 7 studies including 4,629 patients hs-cTnT at a cut-off of <3ng/L was found to have a sensitivity of 99.7% (95% CI 98.4 – 100.0%) and negative predictive value 99.8% (CI 98.7% – 100.0%). This would have enabled 17.5% of patients to have AMI excluded.

99.7% is a pretty good sensitivity, let’s face it. What’s more, it’s better than 98.2% sensitivity of a 0- and 3-hour high sensitivity troponin (Abbott Architect hs-troponin I), as reported recently in JAMA. In fact, not many diagnostic tests in medicine have such good sensitivity.

Of course, this systematic review is still ongoing and there is more recent evidence to synthesise. However, given the interim results, the question is whether you’d be happy to exclude AMI based on this evidence. And, if not, why not?

I’m not asking these questions to be provocative and I’m not stating a personal opinion. I’m asking these questions to stimulate discussion. I’ll be presenting the systematic review at ICEM on Saturday, 30th June just after 2pm. In the meantime, I’d like to harness the power of social media and invite discussion of these findings and their acceptability for practice, via Twitter.

Please feel free to comment, to question, to criticise. And please use the hashtags #hsTnT and #ICEM2012. My presentation at ICEM has these Twitter feeds embedded so we’ll be checking in with your Tweets, live at ICEM, at the end of the presentation. Thanks in advance for your opinions!

Recently, I published a paper in the Journal of the American College of Cardiology describing a strategy that could rule out acute myocardial infarction (AMI) in over a quarter of patients using a single blood test at the point of presentation.

The strategy relies on the use of the high sensitivity troponin T assay from Roche Diagnostics. This assay has a 99th percentile (the diagnostic cut-off) of 14ng/L but the assay can detect levels way below that, in apparently healthy people. In fact, the assay can be reported down to 3ng/L, which is known as the limit of blank (LoB) of the assay.

We know that high sensitivity troponin assays can quantify levels of troponin below the 99th percentile but, at present, we don’t use that information clinically. It doesn’t matter whether the patient has completely undetectable levels of high sensitivity troponin T (<3ng/L) or levels of anything from 3 to 14ng/L. So long as the level is <14ng/L, it’s normal – and that’s all we need to know to rule out AMI.

Ever since high sensitivity assays became available, we’ve also known that they have a higher diagnostic sensitivity for AMI than previous generation troponin assays, i.e. more of the patients with AMI will have positive results when they first arrive at hospital. Unfortunately, the sensitivity still isn’t good enough to allow us to reassure patients that they’re not having a heart attack without repeating the test a number of hours later – at least, not using the conventional cut-off.

I wondered whether we could use the additional information from levels below the 99th percentile to enable us to rule out AMI in some patients immediately. It makes sense that, if troponin levels slowly begin to rise in the circulation after AMI, there should be detectable levels in the circulation even before the level exceeds the 99th percentile. Perhaps those patients who have absolutely no detectable troponin using this highly sensitive assay could be immediately reassured that they don’t have AMI.

Tobias Reichlin’s seminal publication in the New England Journal of Medicine in 2009 suggests that this strategy may have some mileage. In the online appendix, the sensitivity of high sensitivity troponin T (hs-cTnT) at the 3ng/L cut-off was 100%, i.e. no patients with initially undetectable (<3ng/L) levels had AMI.

We sought to validate that finding. In a prospective diagnostic cohort study, we had serum samples from 703 patients. Among these patients, a hs-cTnT level of <3ng/L had 100% sensitivity and negative predictive value for AMI. We then went on to audit our results after implementing hs-cTnT in the clinical environment. Among 915 patients who underwent 2 or more hs-cTnT tests during their admission at our institution (for any reason), only 1 patient with initially undetectable (<3ng/L) troponin developed a subsequent rise, giving a sensitivity of 99.4%. These findings formed the basis of the publication in the Journal of the American College of Cardiology, at http://www.ncbi.nlm.nih.gov/pubmed/21920261.

Having documented these findings, we were keen to determine whether they would stand up to prospective validation and could be introduced into practice to rule out AMI earlier and enable earlier reassurance for many patients, while reducing unnecessary hospital admissions. We therefore undertook a systematic review.

The systematic review is ongoing but early findings are to be presented at the International Conference on Emergency Medicine in June 2012. From 7 studies including 4,629 patients hs-cTnT at a cut-off of <3ng/L was found to have a sensitivity of 99.7% (95% CI 98.4 – 100.0%) and negative predictive value 99.8% (CI 98.7% – 100.0%). This would have enabled 17.5% of patients to have AMI excluded.

99.7% is a pretty good sensitivity, let’s face it. What’s more, it’s better than 98.2% sensitivity of a 0- and 3-hour high sensitivity troponin (Abbott Architect hs-troponin I), as reported recently in JAMA. In fact, not many diagnostic tests in medicine have such good sensitivity.

Of course, this systematic review is still ongoing and there is more recent evidence to synthesise. However, given the interim results, the question is whether you’d be happy to exclude AMI based on this evidence. And, if not, why not?

(For external opinions, you may want to read the links here and here).

I’m not asking these questions to be provocative and I’m not stating a personal opinion. I’m asking these questions to stimulate discussion. I’ll be presenting the systematic review at ICEM on Saturday, 30th June just after 2pm. In the meantime, I’d like to harness the power of social media and invite discussion of these findings and their acceptability for practice, via Twitter.

Please feel free to comment, to question, to criticise. And please use the hashtags #hsTnT and #ICEM2012. My presentation at ICEM has these Twitter feeds embedded so we’ll be checking in with your Tweets, live at ICEM, at the end of the presentation. Thanks in advance for your opinions!

High sensitivity troponin is a great advance in our ability to diagnose acute coronary syndromes. With high sensitivity troponin, we have the ability to detect acute myocardial infarctions that we simply couldn’t detect previously. Thus, many patients with unstable coronary disease who were previously ‘troponin invisible’ (and were therefore labelled as having unstable angina) will now be identified as having non-ST elevation myocardial infarctions (NSTEMI) thanks to the greater analytical sensitivity of the new assays.

This does come with its own challenges, however. With the increase in true positive results comes an increase in false positive results. The greatest challenge is almost certainly the differentiation of ‘true positive’ acute myocardial infarctions (AMIs) from those with non-coronary troponin elevations and type 2 AMIs.

Far from giving a black and white answer about whether the patient has AMI, hs-troponin puts the thinking back into the diagnosis.

This is a great study from 14 countries in the Asia-Pacific region. It relies on clever selection of a low risk population and serial biomarker testing over two hours to identify a proportion of emergency department patients with suspected cardiac chest pain that can be safely discharged.

The next big questions are (a) is it cost effective? (Steve Goodacre’s RATPAC trial will help to answer that when published in Academic Emergency Medicine in the near future); and (b) can we do better? (High sensitivity troponin assays, in particular, may improve sensitivity and enable a larger proportion of patient to be immediately discharged – but we’ll have to wait and see).